HDL-Mediated Cholesterol Efflux and Plasma Loading Capacities Are Altered in Subjects with Metabolically- but Not Genetically Driven Non-Alcoholic Fatty Liver Disease (NAFLD)

Alessia Di Costanzo; Annalisa Ronca; Laura D'Erasmo; Matteo Manfredini; Francesco Baratta; Daniele Pastori; Michele Di Martino; Fabrizio Ceci; Francesco Angelico; Maria Del Ben; Chiara Pavanello; Marta Turri; Laura Calabresi; Elda Favari; Marcello Arca

doi:10.3390/biomedicines8120625

HDL-Mediated Cholesterol Efflux and Plasma Loading Capacities Are Altered in Subjects with Metabolically- but Not Genetically Driven Non-Alcoholic Fatty Liver Disease (NAFLD)

Biomedicines. 2020 Dec 18;8(12):625. doi: 10.3390/biomedicines8120625.

Authors

Affiliations

¹ Department of Translational and Precision Medicine, Sapienza University of Rome, 00161 Rome, Italy.
² Department of Food and Drug, University of Parma, 43124 Parma, Italy.
³ Department of Chemistry, Life Science, and Environmental Sustainability, University of Parma, 43124 Parma, Italy.
⁴ Department of Clinical, Internal, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy.
⁵ Department of Diagnostic of Radiological, Oncological and Anatomopathological Sciences, Sapienza University of Rome, 00161 Rome, Italy.
⁶ Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy.
⁷ Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00161 Rome, Italy.
⁸ Centro Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, 20133 Milan, Italy.

Abstract

Background. Non-alcoholic fatty liver disease (NAFLD) increases the risk of atherosclerosis but this risk may differ between metabolically- vs. genetically-driven NAFLD. High-density lipoprotein (HDL)-mediated cholesterol efflux (CEC) and plasma loading capacity (CLC) are key factors in atherogenesis. Aims. To test whether CEC and CLC differ between metabolically- vs. genetically-determined NAFLD. Methods: CEC and CLC were measured in 19 patients with metabolic NAFLD and wild-type PNPLA3 genotype (Group M), 10 patients with genetic NAFLD carrying M148M PNPLA3 genotype (Group G), and 10 controls PNPLA3 wild-types and without NAFLD. CEC and CLC were measured ex vivo by isotopic and fluorimetric techniques using cellular models. Results: Compared with Group G, Group M showed reduced total CEC (-18.6%; p < 0.001) as well as that mediated by cholesterol transporters (-25.3% ABCA1; -16.3% ABCG1; -14.8% aqueous diffusion; all p < 0.04). No difference in CEC was found between Group G and controls. The presence of metabolic syndrome further impaired ABCG1-mediated CEC in Group M. Group M had higher plasma-induced CLC than Group G and controls (p < 0.001). Conclusions: Metabolically-, but not genetically-, driven NAFLD associates with dysfunctional HDL-meditated CEC and abnormal CLC. These data suggest that the mechanisms of anti-atherogenic protection in metabolic NAFLD are impaired.

Keywords: cholesterol efflux capacity (CEC); cholesterol loading capacity (CLC); genetic NAFLD; metabolic NAFLD; reverse cholesterol transport (RCT).